1. Field of the Invention
The present invention relates to partially acylated .beta.-cyclodextrins, to a process for their preparation and to their use.
2. The Prior Art
Cyclodextrins are cyclic oligosaccarides which are assembled from 6, 7 or 8 .alpha.(1-4)-linked anhydroglucose units. The .alpha.-cyclodextrins, .beta.-cyclodextrins, or .gamma.-cyclodextrins prepared by the enzymic conversion of starch differ in the diameter of their cavity and are generally suitable for enclosing numerous hydrophobic foreign molecules of varying size. Their applications are limited by their low solubilities, especially in the case of .beta.-cyclodextrin, whose solubility in water at 25.degree. C. is 1.8% w/v.
A common method of increasing the solubility of the cyclodextrins is to carry out chemical derivatization on the free hydroxyl groups. Suitable substituents can be introduced on the individual anhydroglucose units at the 2, 3 and/or 6 positions.
Mixtures of substituted cyclodextrins are characterized by their average degree of substitution (DS value). The DS value indicates the number of substituents which are bonded on average per anhydroglucose. The DS value can be determined, for example, by means of .sup.1 H NMR spectroscopy.
Acylated .beta.-cyclodextrins are disclosed, for example, in A. P. Croft, A. Bartsch, Tetrahedron 39, (1983), pp. 1420-1427.
6-Acyl-.beta.-cyclodextrins are disclosed in K. Mitra, Drug Development and Industrial Pharmacy 18 (15), (1992), 1599-1612. In this publication, the influence of chain length and of the degree of substitution with acyl groups on the complex-forming properties and solubilizing properties of 6-acyl-.beta.-cyclodextrins were investigated using steroids.
Acyl-.beta.-cyclodextrins are also marketed by the company Cyclolab. According to the product data sheet, these compounds contain from 8 to 10 acetyl groups per CD ring, with these acyl groups being predominantly linked to the C6 position of the anhydroglucose. This product thus has a DS of 1.28.
CA 117:258209 and CA 119:145682 also mention the use of acylated cyclodextrins as complexing agents without anything being said about the properties or composition of these cyclodextrin derivatives.
Because of the selective substitution on the O-6 oxygen of the glucoses which is obtained using the known preparation processes, the known acylated cyclodextrins exhibit a comparatively poor solubility and a low capacity for solubilizing substances which are sparingly soluble in water.